Protocol for faecal microbiota transplantation in irritable bowel syndrome: the MISCEAT study - a randomised, double-blind cross-over study using mixed microbiota from healthy donors.

INTRODUCTION: Several studies have demonstrated dysbiosis in irritable bowel syndrome (IBS). Therefore, faecal microbiota transplantation, whose effect and safety have been proven in Clostridioides difficile infections, may hold promise in other conditions, including IBS. Our study will examine the effectiveness of stool transfer with artificially increased microbial diversity in IBS treatment. METHODS AND ANALYSIS: A three-group, double-blind,randomised, cross-over, placebo-controlled study of two pairs of gut microbiota transfer will be conducted in 99 patients with diarrhoeal or mixed type of IBS. Patients aged 18-65 will be randomised into three equally sized groups: group A will first receive two enemas of study microbiota mixture (deep-frozen stored stool microbiota mixed from eight healthy donors); after 8 weeks, they will receive two enemas with placebo (autoclaved microbiota mixture), whereas group B will first receive placebo, then microbiota mixture. Finally, group C will receive placebos only. The IBS Severity Symptom Score (IBS-SSS) questionnaires will be collected at baseline and then at weeks 3, 5, 8, 11, 13, 32. Faecal bacteriome will be profiled before and regularly after interventions using 16S rDNA next-generation sequencing. Food records, dietary questionnaires, anthropometry, bioimpedance, biochemistry and haematology workup will be obtained at study visits during the follow-up period. The primary outcome is the change in the IBS-SSS between the baseline and 4 weeks after the intervention for each patient compared with placebo. Secondary outcomes are IBS-SSS at 2 weeks after the intervention and 32 weeks compared with placebo and changes in the number of loose stools, Bristol stool scale, abdominal pain and bloating, anthropometric parameters, psychological evaluation and the gut microbiome composition. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Thomayer University Hospital, Czechia (G-18-26); study results will be published in peer-reviewed journals and presented at international conferences and patient group meetings. TRIAL REGISTRATION NUMBER: NCT04899869.

Moxibustion for diarrhea in COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease that is often accompanied by diarrhea, patients with symptoms such as diarrhea are more likely to develop severe pneumonia, while diarrhea is the most prominent among atypical symptoms. The incidence of diarrhea in COVID-19 patients is 2.0% to 49.5%. Moxibustion has been proven to have a therapeutic effect on diarrhea; however, there is no high-quality evidence on moxibustion for diarrhea in COVID-19 patients. This study was designed to evaluate the effectiveness and safety of moxibustion for the treatment of diarrhea in patients with COVID-19. METHODS: Randomized controlled trials from December 2019 to December 2021 will be included without restrictions on language or publication date. PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Databases, China National Knowledge Infrastructure, Wanfang database, and VIP database will be searched. Two researchers will independently select studies, extract data and evaluate study quality. Cochrane risk of bias tool for randomized trials will be used to assess the risk of bias of included studies. Statistical analyses will be performed using the Review Manager V.5.3 and stata 14.0. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide evidence for whether moxibustion therapy is beneficial to the treatment of diarrhea in COVID-19. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022302933.

Diosmectite inhibits the interaction between SARS-CoV-2 and human enterocytes by trapping viral particles, thereby preventing NF-kappaB activation and CXCL10 secretion.

SARS-CoV-2 enters the intestine by the spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors in enterocyte apical membranes, leading to diarrhea in some patients. Early treatment of COVID-19-associated diarrhea could relieve symptoms and limit viral spread within the gastrointestinal (GI) tract. Diosmectite, an aluminomagnesium silicate adsorbent clay with antidiarrheal effects, is recommended in some COVID-19 management protocols. In rotavirus models, diosmectite prevents pathogenic effects by binding the virus and its enterotoxin. We tested the trapping and anti-inflammatory properties of diosmectite in a SARS-CoV-2 model. Trapping effects were tested in Caco-2 cells using spike protein receptor-binding domain (RBD) and heat-inactivated SARS-CoV-2 preparations. Trapping was assessed by immunofluorescence, alone or in the presence of cells. The effect of diosmectite on nuclear factor kappa B (NF-kappaB) activation and CXCL10 secretion induced by the spike protein RBD and heat-inactivated SARS-CoV-2 were analyzed by Western blot and ELISA, respectively. Diosmectite bound the spike protein RBD and SARS-CoV-2 preparation, and inhibited interaction of the spike protein RBD with ACE2 receptors on the Caco-2 cell surface. Diosmectite exposure also inhibited NF-kappaB activation and CXCL10 secretion. These data provide direct evidence that diosmectite can bind SARS-CoV-2 components and inhibit downstream inflammation, supporting a mechanistic rationale for consideration of diosmectite as a management option for COVID-19-associated diarrhea.

Evaluation of the Clinical and Laboratory Findings of Asthmatic Children with SARS-CoV-2 Infection.

INTRODUCTION: There are a limited number of studies about the clinical findings of coronavirus infection in pediatric patients with asthma. We aimed to evaluate the clinical and laboratory characteristics of pediatric patients with asthma and healthy children without chronic disease who infected with SARS-CoV-2. METHODS: This is a retrospective, case-control study comparing the asthma diagnosed and healthy children who were diagnosed as COVID-19 in our hospital between March 11 and November 10, 2020. RESULTS: During the study period, 6,205 children were diagnosed with CO-VID-19 in our hospital. Only 54 (0.87%) patients had a diagnosis of asthma. The mean of the age was 10.5 years and 53.7% (n:29) of the patients with asthma were male. Cough, shortness of breath, emesis, and diarrhea were found to be significantly higher in asthma group than in the control group (respectively p = 0.002, 0.000, 0.002, 0.019, 0.015). Patients who were given SABA was significantly higher in asthma diagnosed patients (p = 0.000). Hospitalization was significantly higher in asthma group (p = 0.025), and the duration of hospitalization was significantly higher in control group (p = 0.034). There was no significant difference between the 2 groups in terms of requiring oxygen treatment and in laboratory findings between groups. CONCLUSION: This study revealed that pediatric patients diagnosed with asthma were in a mild clinic. According to these findings, asthma may not affect the course of the COVID-19 in children.

Therapy of diarrhea in COVID-19 with external treatment of traditional Chinese medicine: A protocol for systematic review and meta-analysis.

BACKGROUND: Evaluating the effectiveness and safety of external treatment of traditional Chinese medicine therapy for COVID-19 with diarrhea is the primary purpose of this systematic evaluation program. METHODS: We will search the randomized controlled trials from inception to November 2020. The following database is our focus area: Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), VIP database for Chinese technical Periodicals, and Wanfang Database. We will choose articles published both in Chinese and English. Two reviewers will conduct the study selection, data extraction, and assessment independently. The assessment of risk of bias and data synthesis will be carried out using Review Manager Software V.5.3. RESULTS: The results will provide high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: This studys decision will provide evidence of whether external treatment of traditional Chinese medicine is an effective and safe intervention for coronavirus disease 2019 with diarrhea. REGISTRATION NUMBER: INPLASY2020110095 (DOI number: 10.37766/inplasy2020.11.0095).

Probiotics for treating novel coronavirus with diarrhea: A protocol for systematic review and meta analysis.

BACKGROUND: The study aims to evaluate the efficacy and safety of probiotic therapy for coronavirus disease 2019 with diarrhea. METHODS: The following electronic bibliographic databases will be searched to identify relevant studies from December 2019 to December 2020: MEDLINE, PubMed, Embase, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Technical Periodicals, Wan-fang data, Chinese Biological Medicine Database, and other databases. The search results will not be restricted by language, all included articles were randomized controlled trial. Two independent researchers will conduct article retrieval, de-duplication, filtering, quality assessment, and data analysis through the Review Manager (V.5.3). Meta-analysis, subgroup analysis and/or descriptive analysis were performed on the included data. RESULTS: High-quality synthesis and/or descriptive analysis of current evidence will be provided from outcomes. CONCLUSION: This study will provide the evidence of whether probiotics is an effective and safe intervention for coronavirus disease 2019 with diarrhea.PROSPERO registration number: CRD42020192657.

Successful recovery of COVID-19-associated recurrent diarrhea and gastrointestinal hemorrhage using convalescent plasma.

BACKGROUND: Gastrointestinal symptoms are not rare among coronavirus disease 2019 (COVID-19) patients, but there have been no reports regarding convalescent plasma therapy for the recovery of gastrointestinal problems in COVID-19 patients. CASE PRESENTATION: We present two cases of patients with COVID-19-associated recurrent diarrhea and positive fecal occult blood who successfully recovered after a one-time convalescent plasma administration. CONCLUSION: When COVID-19 patients develop recurrent or refractory gastrointestinal symptoms and fail to respond to the available treatment, alternative therapy with convalescent plasma administration may be considered.

Effect of the administration of Lactobacillus spp. strains on neonatal diarrhoea, immune parameters and pathogen abundance in pre-weaned calves.

Neonatal calf diarrhoea is one of the challenges faced by intensive farming, and probiotics are considered a promising approach to improve calves' health. The objective of this study was to evaluate the effect of potential probiotic lactobacilli on new-born dairy calves' growth, diarrhoea incidence, faecal score, cytokine expression in blood cells, immunoglobulin A (IgA) levels in plasma and faeces, and pathogen abundance in faeces. Two in vivo assays were conducted at the same farm in two annual calving seasons. Treated calves received one daily dose of the selected lactobacilli (Lactobacillus reuteri TP1.3B or Lactobacillus johnsonii TP1.6) for 10 consecutive days. A faecal score was recorded daily, average daily gain (ADG) was calculated, and blood and faeces samples were collected. Pathogen abundance was analysed by absolute qPCR in faeces using primers directed at Salmonella enterica, rotavirus, coronavirus, Cryptosporidium parvum and three Escherichia coli virulence genes (eae, clpG and Stx1). The faecal score was positively affected by the administration of both lactobacilli strains, and diarrhoea incidence was significantly lower in treated calves. No differences were found regarding ADG, cytokine expression, IgA levels and pathogen abundance. Our findings showed that oral administration of these strains could improve gastrointestinal health, but results could vary depending on the calving season, which may be related to pathogen seasonality and other environmental effects.

Tuina (massage) therapy for diarrhea in COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: In the beginning of December 2019, the novel coronavirus pneumonia was first detected in Wuhan, China. Its widespread infectivity and strong pathogenicity has posed a great threat to public health, seriously affecting social production and life. Accumulating evidence suggests that gastrointestinal symptoms, such as diarrhea, are common among patients with COVID-19. Tuina (massage) therapy is 1 of the widely employed complementary and alternative medicine interventions in the world. It can act on the subcutaneous muscular layer, enhance the local blood circulation and tissue metabolism of the skin, thus exert its effects on digestive systems and alleviate aversive diarrhea symptoms. This systematic review and meta-analysis will summarize the current evidence of tuina (massage) used as an intervention for diarrhea symptoms in COVID-19. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness and safety of massage therapy in treating exercise-induced fatigue: China National Knowledge Infrastructure, Wanfang and Pubmed Database, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, Excerpta Medica database and MEDLINE. Each database will be searched from inception to June 2020. The entire process will include study selection, data extraction, risk of bias assessment and meta-analyses. RESULTS: This proposed study will evaluate the effectiveness and safety of massage therapy for diarrhea symptoms in COVID-19 patients. The outcomes will include the improvement of diarrhea symptoms and adverse effect. CONCLUSIONS: This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for diarrhea symptoms in COVID-19 patients.Dissemination and ethics: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process.

Diarrhoea and the COVID-19 pandemic.

The new COVID-19 pandemic has been initially linked to respiratory manisfestations. However, there is increasing evidence that other systems are affected by SARS-CoV2; one of which is the gastrointestinal system with several organ-related symptoms and possible implications on prognosis and spread. Diarrhoea is one of the main symptoms of gastrointestinal involvement. In this review the mechanisms, characteristics, prognostic significance and managment of of COVID-19 related diarrhoea are discussed. The possibility of faecal transmission of disease is reviewed.

Diarrhea During COVID-19 Infection: Pathogenesis, Epidemiology, Prevention, and Management.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechanism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research.